Gender differences in VLDL1 and VLDL2 triglyceride kinetics and fatty acid kinetics in obese postmenopausal women and obese men.

CONTEXT: High plasma triglycerides (TG) have been shown to be independent and better predictors of cardiovascular disease than low-density lipoprotein (LDL) cholesterol in women. This may be due to gender differences in very-low-density lipoprotein 1 (VLDL(1))- and VLDL(2)-TG and fatty acid kinetics. OBJECTIVE: Our objective was to investigate whether there are differences in VLDL(1)- and VLDL(2)-TG and fatty acid kinetics in obese men and postmenopausal women, a high risk group for cardiovascular disease. RESEARCH DESIGN AND METHODS: Stable isotopes techniques were used to measure fasting palmitate rate of appearance, metabolic clearance rate, oxidation rate, and nonoxidative disposal rate, VLDL(1)-TG and VLDL(2)-TG fractional catabolic rate (FCR) and production rate (PR). Whole-body fat distribution was measured by magnetic resonance imaging. PARTICIPANTS: Participants included 10 postmenopausal obese women and eight obese men matched for age, body mass index, and fasting plasma TG. RESULTS: The women had lower visceral fat and higher sc fat than the men (P < 0.001 and P < 0.002). Palmitate rate of appearance, metabolic clearance rate, nonoxidative disposal rate, and oxidation rate corrected for resting energy expenditure were greater in the women than the men (all P < 0.03). VLDL(2)-TG PR corrected for fat-free mass was higher in the women (P < 0.001). VLDL(2)-TG and VLDL(2)-cholesterol pools were higher in the women (P < 0.001 and P < 0.008). VLDL(1)-TG FCR and PR and VLDL(2)-TG FCR were not different between genders. CONCLUSION: Fatty acid and VLDL(2)-TG flux is higher in postmenopausal obese women than in obese men matched for fasting plasma TG levels.

Fatty acid flux and oxidation are increased by rimonabant in obese women.

This study aimed to determine in obese women if endocannabinoid receptor antagonism has effects on fatty acid and triglyceride metabolism and insulin sensitivity which are independent from the metabolic effects of weight loss. Fourteen obese (BMI=33.0±0.5 kg/m(2)) (mean±SEM) Caucasian post-menopausal women, aged 57.8±4.7 years were studied. The women were randomised to 2 groups, one group received the endocannabinoid receptor antagonist rimonabant (20 mg/d) for 12 weeks. A control group achieved the same weight loss by a hypocaloric dietary intervention over 12 weeks. Palmitate production rate (Ra), a measure of lipolysis, and palmitate oxidation rate, and VLDL(1) and VLDL(2) triglyceride (TG) kinetics, were measured using isotopic tracers before and after the intervention. Weight loss was not different in the 2 groups; 2.6±0.5 kg with rimonabant and 3.1±1.0 kg in the control group. Palmitate Ra increased with rimonabant with no change in the control group (p=0.03 between groups). Palmitate oxidation rate increased with rimonabant but decreased in the control group (p=0.005 between groups). VLDL(1) TG secretion rate decreased in the control group and increased in the rimonabant group (p=0.008 between groups). There was no significant effect on insulin sensitivity. This study suggests that endocannabinoid receptor antagonism for 12 weeks in obese women increased lipolysis and fatty acid oxidation. The increase in VLDL(1) TG secretion rate may be due to the increase in lipolysis which exceeded the increase in fatty acid oxidation.

Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes.

OBJECTIVE: Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure. RESEARCH DESIGN AND METHODS: A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured. RESULTS: After 16 weeks, weight change was -0.69±1.85 kg with insulin detemir and +1.7±2.46 kg with NPH insulin (P<0.001). Total energy intake was significantly less with insulin detemir (2,016±501 kcal/day) than with NPH insulin (2,181±559 kcal/day) (P=0.026). There was no significant difference in any measure of energy expenditure, HbA1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P=0.039, P=0.047). After the meal, ghrelin and pancreatic polypeptide levels (P=0.002, P=0.001) were higher with insulin detemir. CONCLUSIONS: The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.